In the United States, heart disease is the leading cause of death in both men and women. Several causative factors are implicated in the development of cardiovascular disease including hereditary predisposition to the disease, gender, lifestyle factors such as smoking and diet, age, hypertension, and hyperlipidemia, including hypercholesterolemia. Several of these factors, particularly hyperlipidemia and hypercholesteremia (high blood cholesterol concentrations) provide a significant risk factor associated with atherosclerosis.
Atherosclerosis is associated with an inflammatory response caused by the accumulation of low-density lipoprotein (LDL) molecules in blood vessels. It can be asymptomatic for years. Atherosclerosis causes hardening and narrowing of blood vessels. There are several treatments for atherosclerosis, such as lifestyle change, medication and medical procedures. Statins are a well-known treatment for atherosclerosis. Statins have proven to reduce cardiac risk however the withdrawal of statin therapy abrogrates the protective effect (Heeschen et al. Circulation. 105:1446-1452, 2002).
The current approach to treating atherosclerosis is to provide earlier intervention and life-long treatment. This approach is problematic as it requires identifying asymptomatic patients early in their life cycle and, since risk increases with age, maintaining therapy for the duration of their life. Further, the most efficacious currently available therapies are unable to prevent major cardiac events in all patients whether as primary or secondary interventions. Therefore, there is a need for therapies that can provide rapid benefit in reducing atherosclerosis and have long-term effects that do not require constant administration. The compositions and methods disclosed herein provide an atherosclerosis therapy with sustained therapeutic effects even after the treatment is withdrawn.